Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi.

Edgar M Medina,Jan M Skotheim,Jonathan J Turner,Nicolas E Buchler,Raluca Gordân

doi:10.7554/elife.09492

Abstract

Although cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Here, we show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of the SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi. We hypothesize that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, we show that SBF can regulate promoters with E2F binding sites in budding yeast.

Highlights

The networks regulating cell division in yeasts and animals are highly similar in both physiological function and network structure (Figure 1) (Cross et al, 2011; Doonan and Kitsios, 2009)
Our results indicate that last eukaryotic common ancestor (LECA) likely had complex cell cycle regulation involving at least one cyclin dependent kinase (Cdk), multiple cyclin families, activating and inhibitory E2F transcription factors, and pRb-family pocket proteins
In contrast to the growing consensus that LECA had an extensive repertoire of proteins, the prevailing view of the cell cycle in LECA is that it was based on a simple oscillator constructed with relatively few components (Coudreuse and Nurse, 2010; Nasmyth, 1995)

Summary

Introduction

The networks regulating cell division in yeasts and animals are highly similar in both physiological function and network structure (Figure 1) (Cross et al, 2011; Doonan and Kitsios, 2009). The cell cycle controls proliferation in response to a variety of internal and external signals during the G1 phase, between cell division and DNA replication. These input signals, including cell growth, are integrated into a gradual increase in cyclin dependent kinase (Cdk) activity, which triggers a feedback loop at the basis of the all-or-none irreversible decision to proliferate (Bertoli et al., 2013). Many of the molecular mechanisms underlying G1 regulation are highly conserved. This begins the inactivation of pRb and the concomitant activation of the E2F transcription factors that induce transcription of downstream cyclins E and A, which complete the inhibition of pRb thereby forming a positive feedback loop (Bertoli et al, 2013)

Methods

Results

Conclusion